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Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
Published on: May 31, 2024
Therapeutic potential of otilonium bromide against Vibrio vulnificus
1College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
Abstract:
New drugs are urgently required for the treatment of infections due to an increasing number of new strains of diseases-causing pathogens and antibiotic-resistant bacteria. A library of drugs approved by Food and Drug Administration was screened for efficacy against Vibrio vulnificus using antimicrobial assays. We found that otilonium bromide showed potent antimicrobial activity against V.vulnificus and had a synergistic effect in combination with antibiotics. Field emission transmission electron microscope images revealed that otilonium bromide caused cell division defects in V.vulnificus. Moreover, it significantly inhibited V.vulnificus swarming motility and adhesion to host cells at concentrations lower than the minimum inhibitory concentration. To investigate its inhibitory action mechanisms, we examined the effect of otilonium bromide on the expression levels of several proteins crucial for V.vulnificus growth, motility, and adhesion. It decreased the protein expression levels of cAMP receptor protein and flagellin B, but not HlyU or OmpU. In addition, otilonium bromide significantly decreased the expression levels of outer membrane protein TolCV1, thus inhibiting RtxA1 toxin secretion and substantially reducing V.vulnificus cytotoxicity to host cells. Collectively, these findings suggest that otilonium bromide may be considered as a promising candidate for treating V.vulnificus infections.
Insights
Otilonium bromide demonstrates potent antimicrobial activity against Vibrio vulnificus, inhibiting its growth and virulence. This drug shows promise as a new therapeutic option for treating Vibrio vulnificus infections.
Area of Science:
- Microbiology
- Drug Discovery
Background:
- Emerging drug-resistant pathogens necessitate novel antimicrobial agents.
- Vibrio vulnificus infections pose a significant public health threat.
Purpose of the Study:
- To screen Food and Drug Administration-approved drugs for efficacy against Vibrio vulnificus.
- To investigate the antimicrobial mechanisms of otilonium bromide against Vibrio vulnificus.
Main Methods:
- Antimicrobial assays were used to screen a drug library.
- Field emission transmission electron microscopy and protein expression analysis were employed.
- Swarming motility and host cell adhesion assays were conducted.
Main Results:
- Otilonium bromide exhibited potent antimicrobial activity and synergistic effects with antibiotics against Vibrio vulnificus.
- It induced cell division defects, inhibited swarming motility, and reduced host cell adhesion.
- Mechanism of action involves downregulating cAMP receptor protein, flagellin B, and TolCV1, thereby reducing RtxA1 toxin secretion and cytotoxicity.
Conclusions:
- Otilonium bromide is a potential candidate for treating Vibrio vulnificus infections.
- Its multifaceted inhibitory action on bacterial virulence factors warrants further investigation.
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